Significant physiological adaptations are required for successful newborn transition to life outside the womb. These include major cardiovascular, pulmonary and metabolic alterations. Ample evidence exists to suggest that neurosympathetic system activation is vital to these adaptive changes. We have developed the ability to support a premature lamb in the extrauterine environment in much the same fashion as we would a premature infant. This model and highly sensitive methods to measure plasma and tissue catecholamine levels make it possible to further explore the role of catecholamines, the hormone-neurotransmitters released by the neurosympathetic system, in the circulatory and metabolic alterations occurrring in the newborn period. We will examine the magnitude of catecholamine release at the time of birth at several developmental ages, measure catecholamine production rates and clearance rates, and measure the thresholds for circulatory and metabolic effects. Preliminary evidence suggests that part of the disproportionately higher newborn mortality in male infants is due to delayed neurosympathetic maturation relative to female infants. We plan to examine sex differences in catecholamine physiology to support or refute this hypothesis. The specific aims of the present project will provide valuable insights into the mechanisms of newborn adaptation. A better understanding of these mechanisms will allow development of strategies for augmentation of neurosympathetic control or pharmacologic manipulation of the neurosympathetic system which will improve survival of the premature infant as well as the compromised term infant.